Purchase this article with an account.
N. Piri, J.M. K. Kwong, M. Song, J. Caprioli; Gene Expression in Glaucomatous Retinas Implicate the TNF–Mediated Pathway in Retinal Ganglion Cell Death . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1245.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Identification of apoptotic mechanisms associated with retinal ganglion cell (RGC) death in glaucomatous retinas. Methods: A rat glaucoma model was generated with chronic, moderately elevated intraocular pressure (IOP). The number of surviving cells in the ganglion cell layer (GCL) was estimated to evaluate the extent of RGC degeneration in the retinas of these animals. Gene expression profiles of the control and treated retinas were obtained with oligonucleotide microarrays that represent 22,000 genes and expressed sequence tags (ESTs). Data obtained from microarray experiments (n=3 for each time point) were clustered and analyzed with Microsoft Excel, EASE: the Expression Analysis Systematic Explorer, and Pathway Assist softwares. Real–time quantitative PCR and semi–quantitative RT–PCR were used to validate the changes in gene expression levels observed by the microarrays. Results: The comparison of gene expression profiles obtained from the retinas two and five weeks after IOP elevation revealed 121 genes (24 of them have been characterized), the expressions of which were similarly affected. Corresponding proteins with known functions were clustered, based on their roles in biological processes with EASE software, and analyzed with the Pathway Assist software package to determine their interactions with other proteins and to build biological association networks. We found that 8 out of the 24 characterized genes, including guanylate kinase–interacting protein, hemopexin, and transcription factors NR2F2 (nuclear receptor subfamily 2), ELK1 (Ets family of transcription factors), BF–1 (proto–oncogene brain factor–1) are associated with tumor necrosis factor (TNF), mitogen–activated protein kinase 8 (MAPK8), and MAPK kinase kinase (MAP3K). TNF, MAPK8, and MAP3K are essential factors in the TNF–mediated apoptotic pathway. Conclusions: Results of the gene expression profiling obtained from the retinas after IOP elevation suggest that TNF–mediated apoptotic cell death is an important mechanism involved in RGC degeneration in glaucomatous retinas.
This PDF is available to Subscribers Only